Fig. 1.

R16 and R17 fold on an energy landscape with two sequential transition states (TSs) and a high‐energy intermediate. At low concentrations of denaturant, the rate‐limiting transition state is TS1.¹³ At TS1, helices A and C dock, establishing the correct topology and register of the long spectrin helices. At TS2, structure condenses and the B-helix starts to pack.^4,5 It is the folding and unfolding over TS1 that is investigated in this study. The landscape at TS1 is rough and this roughness slows folding by about 5-fold.^6,14 At TS2, there is no evidence for roughness in the energy landscape (B. G. Wensley and J. Clarke, unpublished data).